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Cortical gene transcription response patterns to water maze training in aged mice

Sung-Soo Park1, Alexis M Stranahan2, Wayne Chadwick1, Yu Zhou1, Liyun Wang1, Bronwen Martin3, Kevin G Becker4 and Stuart Maudsley1*

Author Affiliations

1 Receptor Pharmacology Unit, National Institute on Aging, Baltimore, MD 21224 USA

2 Physiology Department, Georgia Health Sciences University, 1120 15th St., Augusta, GA, 30912 USA

3 Metabolism Unit, National Institute on Aging, Baltimore, MD 21224 USA

4 Gene Expression and Genomics Unit, Research Resources Branch, National Institute on Aging, Baltimore, MD 21224 USA

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BMC Neuroscience 2011, 12:63  doi:10.1186/1471-2202-12-63

Published: 29 June 2011



The hippocampus mediates the acquisition of spatial memory, but the memory trace is eventually transferred to the cortex. We have investigated transcriptional activation of pathways related to cognitive function in the cortex of the aged mouse by analyzing gene expression following water maze training.


We identified genes that were differentially responsive in aged mice with accurate spatial performance during probe trials or repeated swimming sessions, relative to home cage conditions. Effective learners exhibited significantly greater activation of several pathways, such as the mitogen-activated protein kinase and insulin receptor signaling pathways, relative to swimmers. The genes encoding activity-related cytoskeletal protein (Arc) and brain-derived neurotrophic factor (BDNF) were upregulated in proficient learners, relative to swimmers and home cage controls, while the gene encoding Rho GTPase activating protein 32 (GRIT) was downregulated. We explored the regulation of Arc, BDNF, and GRIT expression in greater morphological detail using in situ hybridization. Recall during probe trials enhanced Arc expression across multiple cortical regions involved in the cognitive component of water maze learning, while BDNF expression was more homogeneously upregulated across cortical regions involved in the associational and sensorimotor aspects of water maze training. In contrast, levels of GRIT expression were uniformly reduced across all cortical regions examined.


These results suggest that cortical gene transcription is responsive to learning in aged mice that exhibit behavioral proficiency, and support a distributed hypothesis of memory storage across multiple cortical compartments.